HETEROCYCLES
An International Journal for Reviews and Communications in Heterocyclic ChemistryWeb Edition ISSN: 1881-0942
Published online by The Japan Institute of Heterocyclic Chemistry
Regular Issue
Vol. 36, No. 10, 1993
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■ Synthesis of Highly Substituted Pyridines through Nucleophilic Substitution of Tetrachloro-3-cyanopyridine
Sergei V. Chapyshev and Toshikazu Ibata*
*Institute of Chemistry, College of General Educatin, Osaka University, Toyonaka, Osaka 560-8531, Japan
Abstract
Tetrachloro-3-cyanopyridine reacts with anilines and/or sodium azide through replacement of three chlorine atoms at the 2-, 4-, and 6-positions, whereas with difunctional nucleophiles by replacement of chlorines at the 5- and 6-positions. Using these reactions synthesis of highly substituted pyridines has been developed.
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■ Isolation of Novel Meso-substituted Uroporphyrins from Cultures of Pseudomonas
Wen Lin, Robert S. Burkhalter, and Russell Timkovich*
*Department of Chemistry, University of Alabama, Box 870336, University, Tuscaloosa, Alabama 35478-0336, U. S. A.
Abstract
Two novel and unusal porphyrins have been isolated from the pool of porphyrin metabolites in cultures of Pseudomonas. They correspond to substitution of a meso proton in uroporphyrin by a nitro group or a chlorine atom. The purified compounds have been characterized by 1H-nmr, mass spectrometry, and visible spectroscopy to establish their structure.
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■ Dicarbonyl(η5-cyclopentadienyl)iron-(II)-η1-complexes of Carbohydrates
Jozua F. Booysen, Martin W. Bredenkamp,* and Cedric W. Holzapfel
*Department o f Chemistry and Biochemistry, Rand Afrikaans University, P.O. Box 524, Auckland Park, 2006, Johanesberg, South Africa
Abstract
Dicarbonl(η5-cyclopentadienyl)iron(II) η1-complexes of carbohydrates are prepared by reaction of 2-deoxy-2-halosugars with sodium dicarbonyl(η5-cyclopentadienyl)ferrate via a single-electron-transfer mechanism. Evidence for the in situ conversion of these compounds into the corresponding thermo-labile dicarbonyl(η5-cyclopentadienyl)iron(II) η2-complexes, is presented.
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■ Ring Expansion of Spirocyclic Dithioketals via 1,3-Sulfur Migration by the Mitsunobu Reaction
Seiichi Takano,* Hirokazu Iida, and Kunio Ogasawara
*Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Abstract
Treatment of the spirocyclic dithioketals of some β-hydroxy ketone derivatives with diisopropyl azodicarboxylate and triphenylphosphine furnished the ring-expanded products via 1,3-sulfur migration.
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■ (-)-Corydecumbine, a Novel Phthalideisoquinoline Alkaloid from Corydalis decumbens
Purusotam Basnet, Shigetoshi Kadota,* Jian Xin Li, Chun Zhen Wu, and Tsuneo Namba
*Research Institute for Wakan-Yaku, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, Toyama 930-0194, Japan
Abstract
A novel alkaloid, (-)-corydecumbine (1) was isolated from the cultivated tuber of Corydalis decumbens (Thunb.) Pers. (Papaveraceae) and the structure was determined by the use of 2D nmr.
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■ A New Synthesis of Streptomyces Lactones by 1,3-Dipolar Cycloaddition
Ugo Chiacchio, Maria R. Di Bella, Antonio Rescifina, Giovanni Romeo,* and Nicola Uccella
*Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy
Abstract
The cycloaddition of nitrones (4) to propene, followed by sequential treatment with methyl trifluoromethanesulfonate, H2-Pd/C, and m-chloroperbenzoic acid, is shown to provide a general method for the preparation of a variety of volatile streptomyces lactones.
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■ Mannich Reactions of Indoles with Dichloromethane and Secondary Amines under High Pressure
Kiyoshi Matsumoto,* Takane Uchida, Shiro Hashimoto, Yukie Yonezawa, Hirokazu Iida, Akikazu Kakehi, and Shinichi Otani
*Graduate School of Human and Environmental Studies, Kyoto University, Yoshida-Nihonmatsu-cho, Sakyo-ku, Kyoto 606-8501, Japan
Abstract
Mannich reactions of indole with dichloromethane and secondary amines gave the corresponding Mannich bases in moderate to good yield, while 2-methylindole afforded only low yields of the Mannich bases. Some limitations were observed in the cases of hindered amines and 2-phenylindole.
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■ Bullacin: A New Cytotoxic Annonaceous Acetogenin from Annona bullata
Zhe-ming Gu, Xin-ping Fang, Lu Zeng, Karl V. Wood, and Jerry L. McLaughlin*
*Department of Medicinal Chemistry and Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette IN 47907, Indiana 47907, U.S.A.
Abstract
Using the brine shrimp lethality test (BST) to direct fractionation, two additional Annonaceous acetogenins, bullacin (1) and parviflorin (2), were isolated from the ethanol extract of the bark of Annona bullata Rich. Their absoulte stereochemistries were revealed by the use of Mosher’s methodology. Compound (1) is a new adjacent bis-tetrahydrofuran (THF) acetogenin possessing a relatively rare C35 skeleton and an unprecedented C-6 hydroxyl group. The absolute configuration of 1 was assigned as 6S, 13R, 14R, 17R, 18R, 21R, 22R, and 34S. Compound (2) is a known acetogenin but is new to this plant. The absolute configuration of 2 was concluded to be 4R, 13R, 14R, 17R, 18R, 21R, 22R,and 34S. This is the first paper in which the absolute stereochemistry of a new acetogenin is published with the new structure. 1 showed 10 to 1000 times the cytotoxic potency of adriamycin when tested in human tumor cell lines.
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■ The Regiospecific Synthesis of ortho Aminonaphthophenones via the Addition of Carbanions to Naphthoxazin-4-ones
Weijiang Zhang, Ruiyan Liu, and James M. Cook*
*Department of Chemistry, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, U.S.A.
Abstract
The conversion of nitronaphthalenes (see 4a and 4b) into the corresponding ortho aminonaphthylnitriles (5a and 5b) via the process of Tomioka, when combined with the addition of carbanions to the intermediate naphthoxazin-4-ones, provided a route to ortho aminonaphthophenones (7a) and (7b). These key intermediates were employed to synthesize the benzfused 2’-fluoro-1,4-benzodiazepines (1-3).
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■ An Expeditiuos Total Synthesis of (+)-Blastmycinone
Kiyoharu Nishide, Atsunori Aramata, Teruki Kamanaka, and Manabu Node*
*Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan
Abstract
Asymmetric γ-methylation of tetronic acid using (S)-2-methoxymethylpyrrolidine as a chiral auxiliary and its application to the total synthesis (+)-blastmycinone (1) were described.
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■ A Synthesis of 3,4-Disubstituted Indoles
Géza Galambos, Csaba Szántay Jr., József Tamás, and Csaba Szántay*
*Central Research Institute for Chemistry, Hungarian Academy of Sciences, H-1025 Budapest, Pusztaszeri ut 59-67, P.O.Box 17, Hungary
Abstract
3,4-Disubstituted indoles are prepared through palladium-catalyzed coupling.
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■ A New Route to 1-Azaazulene Ring System by the Reaction of 1-(Diphenylphosphinyl)azaallyl Anions with Tropone Derivatives
Koji Ito and Makoto Nitta*
*Department of Chemistry, School of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan
Abstract
The reaction of 1-(diphenylphosphinyl)azaallyl anions, derived from the corresponding imines, with tropones underwent enamine-type alkylation and mainly followed by aza-Wittig reaction to give 1-azaazulene derivatives, in addition to a trace amount of 4H-4-oxocyclohepta[b]pyrroles.
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■ Iminophosphorane-mediated Synthesis of Oxazole Alkaloids: One-Step Preparation of O-Methylhalfordinol and Annuloline
Pedro Molina,* Pilar M. Fresneda, and Pedro Almendros
*Departamento de Química Orgánica, Facultad de Química, Universidad de Murcia, Campus de Espinardo, E-30071, Murcia, Spain
Abstract
The three-component reaction between triphenylphosphine, 4-methoxyphenacyl azide and nicotinoyl chloride or 3,4-dimethoxycinnamoyl chloride leads directly in good yields to O-methylhalfordinol or annuloline respectively.
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■ A Short Synthesis of Potential Juvenoids Based on the Isoxazole Chemistry
Lourdes Martin, Cecilia Polo, Vicente Ramos, Tomás Torroba,* and Stefano Marcaccini
*Departamento de Química Orgánica, Facultad de Veterinaria, Universidad de Extremadura, E-10071 Cáceres, Spain
Abstract
3,4,5-Trisubstituted isoxazoles (1) and (4) afforded, after chromic oxidation and borohydride reduction, (±)-3-methyl-6-(3-methyl-5-phenylisoxazol-4-yl)-6-hydroxyhexanoic acid (2) or (±)-1-(3-methyl-5-phenylisoxazol-4-yl)-3,4-dihydro-1H-2-benzopyran-3-ona (5) which were reduced to (±)-(Z/E)-3-methyl-7-benzoyl-8-oxonon-6-enoic acid (3) and (E)-2-(2-[2-benzoyl-3-oxobut-1-enyl]phenyl)acetic acid (6) with molybdenum hexacarbonyl. Lactone (5) afforded a single E-diastereoisomer of acid (6). Catalytic hydrogenation of 5 afforded selectively isoxazole (7) which was reduced with molybdenum hexacarbonyl to 2-(2-[2-benzoyl-3-oxobutyl]phenyl)acetic acid (8). Structures of products are related with those of some juvenoids.
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■ Synthesis of Pyrazolidin-3-ones from α,β-Unsaturated Sugar Lactones and Hydrazine
Irma Panfil and Marek Chmielewski*
*Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, P.O.Box 58, PL-01-224 Warszawa 42, Poland
Abstract
Conjugate addition - cyclization of hydrazine to δ-lactones (2, 3, and 6) provides the respective pyrazolidin-3-ones as single products. The addition proceeds anti to the terminal carbon atom of the sugar lactone.
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■ Synthesis of 4-Amino-8-cyanoquinazolines from Enones and Enals
Pedro J. Victory,* José I. Borrell, Anton Vidal-Ferran, Elvira Montenegro, and M. Luisa Jimeno
*Departament de Química Organica, CETS Institut Químic de Sarria, Universitat Ramon Llull, Via Augusta 390, E-08017 Barcelona, Spain
Abstract
The treatement in a sodium methoxide/methanol solution of α,β-unsaturated enones or aldehydes with propanedinitrile in a 1:2 molar ratio led to 2-aminobenzene-1,3-dicarbonitriles. These compounds afforded 4-amino-8-cyanoquinazolines by reaction with formamide or guanidine.
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■ Synthesis with Nitriles: 92. Synthesis of 5-Formylcytosine Derivatives
Madhukar Jachak,* Martin Mittelbach, and Hans Junek
*Institute for Organic Chemistry,University Graz, Heinrichstrbe. 28, A-8010 Graz, Austria
Abstract
The reactivity of 3-dimethylamino-2-formylpropenenitrile (1) with various amino compounds is studied. Thus, condensation of 1 with anilines gives the corresponding azomethines (2a-c). Reaction of 1 with thiourea and guanidine resp., leads to 5-formylthiocytosine (3) and 2-amino-5-cyanopyrimidine (4). The 2-formyl-3-ureidopropenenitriles (5a-i) can be obtained by reaction of 1with urea and substituted ureas. 5a-i can easily be cyclized to 3-substituted 5-formylcytosines (6a-e). Condensation of 6 with aniline, benzylamine and phenylhydrazine leads to the azomethines (7a-i). Pyrido[2,3-d]pyrimidine-6-carbonitriles (8a, 8b, 8d and 8e) are obtained by reaction of 6 with malononitrile.
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■ An Efficient Procedure for the Synthesis of Pyrazolo]3,4-d][1,3]thiazine-4-ones
Chiara B. Vicentini, Augusto C. Veronese, Salvatore Guccione, Mario Guarneri, Maurizio Manfrini, and Paolo Giori*
*Dipartimento di Scienze Farmaceutiche, Università di Ferrara, via Fossato di Mortara 17, I-44100, Ferrara, Italy
Abstract
Trichloromethyl chloroformate reacts with N-(1-alkyl/aryl-5-pyrazolyl)thiocarboxamides (2a-j) to give pyrazolo[3,4-d][1,3]thiazin-4-ones (3) while it reacts with N-(3-methyl-5-pyrazolyl)thiobenzamide (2m) to give the pyrazolo[1,5-c][1,3,5]thiadiazine-4-one (4). Heating under reflux in formic acid of homologues (3g-i) bearing a tert-butyl group linked to pyrazole N-1 atom afforded the dealkylated derivatives (3k-m).
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■ Heterocyclic Systems: Synthesis and Reactivity of Thieno[2,3(3,2)-b]indolizidin-9-ones
Dominique Lebosquain and Bernard Decroix*
*Laboratoire de Chimie, UER des Sciences et Techniques, Université du Havre, 30, rue Gabriel Péri, 76600 Le Havre,France
Abstract
A simple and efficient synthesis of thieno[2,3(3,2)-b]indolizidin-9-ones is described starting from 2(3)-halogenomethylthiophene. The reactivity (Beckmann and Schmidt rearrangements) of these ketones is studied and compared with the reactivity of thienoquinolizidinones and thienoindolizidinediones
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■ Synthesis of 2,5,8(1H)-Quinolinetrione Derivatives through Vilsmeier-Haack Formylatioin of 2,5-Dimethoxyanilides
Miguel Angel Alonso, Ma del Mar Blanco, Carmen Avendaño,* and J. Carlos Menéndez
*Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Ciudad Universitaria, 28040 Madrid, Spain
Abstract
The preparation of 2,5,8(1H)-quinolinetrione derivatives bearing both electron-withdrawing and electron-releasing groups at C3 is described. The reaction sequence employed involves Vilsmeier-Haack cyclization of 2,5-dimethoxyanilides into 3-substituted 5,8-dimethoxy-2-chloroquinolines, followed by hydrolysis to the corresponding 2(1H)-quinolinones and oxidative demethylation with cerium ammonium nitrate.
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■ Synthesis and Serotonergic Activity of 8-[4-(2,3-Dihydro-1,4-dioxino[2,3-b]pyridin-2-yl-methylamino)butyl]-8-azaspiro[4,5]decane-7,9-dione
Abdelhakim Benarab and Gerald Guillaumet*
*Laboratoire de Chimie Bioorganique et Analytique, URA-CNRS N° 499, Université d’Orléans, BP 6759, Rue de Chartres, 45067 Orleans Cedex 2, France
Abstract
The synthesis of compound (9), a nitrogen-containing bioisostere of the 1,4-benzodioxane moiety of the MDL 72832, is detailed. This compound showed a moderate affinity for the 5-HT1A receptors.
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■ Application of the Photo-Fries Rearrangement of Aryl N-Chloroacetylanthranylates as Key Step in the Synthesis of 5-(2-Hydroxyphenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-ones
Felipe Algarra and Miguel A. Miranda*
*Departamento de Química/Instituto de Tecnología Química, UPV-CSIC, Universidad Politécnica de Valencia, Apartado 22012, E-46071 Valencia, Spain
Abstract
Condensation of isatoic anhydride with phenols, followed by treatment of the resulting aryl anthranylates (4) with chloroacetyl chloride gives aryl N-chloroacetylanthranylates (5). Their uv-irradiation results in photo-Fries rearrangement, to afford benzophenones (6). Direct treatment of the latter with ammonia gives rise to 1,3-quinazolines (7); by contrast, treatment of 6 with potassium iodide and subsequently with ammonia leads to 1,3-dihydro-2H-1,4-benzodiazepin-2-ones (1).
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■ Photocyclization of Enamides. 38. Reductive Photocyclization of α-(Methylthio)- and α-(Arylthio)enamides
Takeaki Naito,* Hiromi Tanada, Yumiko Suzuki, Haruko Saito, Toshiko Kiguchi, and Ichiya Ninomiya
*Kobe Women's College of Pharmacy, Motoyamakita, Higashinada, Kobe 658-8558, Japan
Abstract
Reductive photocyclization of α-(methylthio)enamide (2) gave exclusively six-membered lactams (3) and (4) while the same reaction of α-(arylthio)enamides (6) and (12) was found to afford five-membered lactams (7) and (13) as major proucts. A novel total synthesis of (±)-polyzonimine (18b) was accomplished by applying the newly found reductive photocyclization of α-(naphthylthio)enemide leading to the formation of five-membered lactams.
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■ A New Alkaloid, 2-Hydroxy-7-methyl-9H-carbazole from Cimicifuga simplex
Genjiro Kusano,* Makio Shibano, Mayumi Idoji, and Katsuhiko Minoura
*Osaka University of Pharmaceutical Sciences, 2-10-65 Kawai, Matsubara, Osaka 580, Japan
Abstract
A new alkaloid was isolated from the aerial parts of Cimicifuga simplex and was formulated as 2-hydroxy-7-methyl-9H-carbazole on the basis of the spectroscopic evidence.
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■ Complete 1H-Nmr Spectral Assignments of Six 3-Etyl Indolo[2,3-a]quinolizidine N-Oxides. NOE Difference Spectroscopy Applied to Conformational Analysis
Reija Jokela and Mauri Lounasmaa*
*Laboratory for Organic and Bioorganic Chemistry, Technical University of Helsinki, P.O. Box 6100, FIN-02150 HUT Espoo, Finland
Abstract
Complete 1H-nmr spectral assignments of six 3-ethylindole[2,3-a]quinolizidine N-oxides are reported. The predominant conformaions of the compounds were determined by NOE difference spectroscopy.
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■ The Novel Reduction of Pyridine Derivatives with Samarium Diiodide
Yasuko Kamochi* and Tadahiro Kudo
*Daiichi College of Pharmaceutical Sciences, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-0037, Japan
Abstract
Pyridine was rapidly reduced into piperidine with samarium diiodide in the presence of water at toom temperature in excellent yield. On the similar reactions of pyridine derivatives bearing chloro, amino and cyano functionalities with samarium diiodide-H2O-THF system, these functionalities were partly eliminated with this system to afford pyridine or piperidine. Furthermore, pyridinecarboxamides were reduced with this system to give the corresponding methylpyridines and 2-pyridinecarboxylic acid was reduced to give 2-methylpyridine as the major products.
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■ Synthesis of a Key Intermediate for D-Biotin via 1,3-Cycloaddition of a Thiocarbonyl Ylide and Sila-Pummerer Rearrangement
Toru Yamano, Mitsutaka Tanaka, and Kunio Takanohashi*
*Technology Development Laboratories, Takeda Chemical Industries, Ltd., Juso-honmachi, Yodogawa-ku, Osaka 532, Japan
Abstract
An efficient preparation of a d-biotin intermediate, (±)-(3aα,4α,6aα)-1,3-dibenzyl-3a,4,6,6a-tetrahydro-4-hydroxy-1H-thieno[3,4-d]imidazol-2(3H)-one was accomplished by use of 1,3-cycloaddition of a thiocarbonyl ylide, Curtius rearrangement and sila-Pummerer rearrangement. Addition of p-toluenesulfonic acid was found to be effective to promote sila-Pummerer rearrangement of sterically unfavorable anti-2-trimethylsilyl sufoxide.